Fever Flashcards

1
Q

Explain the physiology of thermoregulation

What is thermoregulation?

A

Thermoregulation = mechanism by which mammals maintain a body temperature by tightly controlled self regulation, no matter what the temperature of the surrounding environment is.

Human core temperature - 37 oc

Controlled by the hypothalamus

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2
Q

Physiology of thermoregulation:

What sensors are involved?

A
  • Body has thermal sensors within the skin and body core (mainly the hypothalamus) that respond to changes in their local temperature.
  • Skin receptors ideal for sensing environmental temperature (not internal temp); body core thermoreeptors are ideal for detecting changes in core temperature (not outside environment).
  • Skin thermoreceptors –> warmth and cold receptors that increase firing rate over certain temperature ranges (40> and <40 respectively) –> info sent to hypoT and via thalaus to cerebral cortex (conscious awareness of temp)
  • Core thermoreceptors –> brain, spinal cord, blood vessels and muscle.
  • Preoptic area and anterior hypothalamus particularly involved.
  • Sensory information is fed into the anterior hypothalamus/ preoptic area
  • balances heat production/ heat loss to maintain core body temperature within narrow limits
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3
Q

Physiology of thermoregulation:

Integration centre and efferent part?

A
  • Info from skin thermoreceptors travels via spinal cord to hypoT
  • HypoT integrates thermal information from other parts of the body (including hypoT core temp thermoreceptors) and compares prevailing thermal status to ideal set of thermal conditions
  • directs efferent commands to alter rate of heat generation and modify heat transfer rates
  • Efferents:
    • Vasodilation of cutaneous arterioles (heat transfer to environment) vs vasoconstriction of cutaneous arterioles (minimis heat loss)
    • Eccrine sweat glands –> heat load activates ANS to stimulate sweat secretion onto skin –> heat loss (remember innervation to sweat gland = sympathetic but Ach is neurotransmitter).
    • Shivering –> cold stress stimulates involuntary muscular contractions of skeletal muscle, increase basal metabolic rate.
    • Non shivering thermogenesis in brown adipose tissue –> in newborn infants
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4
Q

Define fever

A

Fever = an abnormal elevation of core temperature as part of a specific biologic response mediated and controlled by the CNS.

CDC defines it as any temperature aobe 38oc.

Current covid guidance = any temp above 37.7

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5
Q

Explain the pathophysiology of fever

What is the purpose of fever?

A
  • Fever caused by action of circulating cytokines called Pyrogens - produced by cells of the immune system
  • Macrophages and lymphocytes release cytokines into the circulation in response to various infectious and inflammatory stimuli
  • act as endogenous pyrogens –> cascade initiated when IL1B interacts with endothelial cells in leaky portion of BBB –> triggers endothelial release of prostaglandin E2 –> diffused to hypothalamus and elevates T set –> initates febrile response
  • Pyrogenic cytokines = IL6/IL1/TNFalpha/IFN gamma/ prostaglandins, phospholipase) –> raised T set in hypoT –> Fever –> raised temp inhibits pathogen reproductiong and facilitates immune response
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6
Q

What are the pathological effects of fever on the body?

A
  • Related to the fact that fever requires more energy to raise core temperature:
    • ↑O2 need, ↑RR, ↑HR, ↑body protein as energy source, ↓glucose ↑protein/fat breakdown.
  • Hypothalamus ability to control thermoregulation becomes impaired
  • cerebral ischaemia and cerebral oedema develop
  • ARDS –> due to hyperventilation, respiratory failure and pulmonary oedema
  • increased burden on the heart –> elevated HR and increased CO
  • GI system –> vulnerable to sepsis and haemorrhage due to stress response
  • Intravascular dehydration
  • AKI due to dehydration and impairment in circulation
  • Leads to electrolyte abnormalities, hypoglycaemia, acid base disturbance secondary to sepsis
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7
Q

Define pyrexia of unknown origin

A

BMJ = Pyrexia of unknown origin = temperature > 38.3 on several separate occasions, duration of fever > 3 weeks ,appropriate initial diagnostic work up which does not reveal cause of the fever.

Oxford handbook definition = temperature of over 38.3 for over 3 weeks without any obvious cause despite investigation

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8
Q

Non infectious causes of fever?

A

Non infective:

malignancy –> leukaemia, fever and night sweats – prognostic of the severity

endocrine à thyrotoxicosis

recreational drugs à amphetamines, cocaine, MDMA

prescribed drugs à ssri AND Serotonin syndrome, drug fever w new drugs

Rheumatological à RA, Gout, IBD,

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9
Q

Common infectious causes of fever?

A

PCP- pneumocystis pneumonia - fungus pneumocystic jirovecii (often linked to HIV / immunosuppression).

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10
Q

What are the causes of fever?

A
  • Divided into infectious and non infectious causes

Noninfectious causes:

  • Connective tissue disorders - polymyalgia rheumatica, SLE, RA
  • Autoimmune - IBD, temporal arteritis, adult onset stills disease
  • Drug reactions - serotonin syndrome, drug fever
  • Malignancy - haemtological, renal, liver, colon etc.
  • Thyrotoxicosis

Infectious cause: acute response to infection - any part of the body where infection can develop e.g :

  • CNS – meningitis, encephalitis, myelitis
  • URTI/LRTI/TB/Pneumonia
  • GI- hepatitis, cholescystitis, gastroenteritis
  • Urological - pyelonephritis, UTI
  • Joints/ bones/ skin - cellulitis/ osteomyelitis/ septic arthritis
  • Viral - HIV/ Covid19
  • Parasite - Malaria/ scabies
  • Fungal - candidaemia - in immunocompromised patients
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11
Q

What is serotonin syndrome and what type of fever does it cause?

A

Serotonin syndrome = excess serotonin in the body leading to severely raised temp above 40oc

Presents with altered mental status (agitation/excitement/confusion/coma), altered meuromuscular excitability (muscle spasms, tremor, rigidity, hyperreflexia) and autonomic instability ( hyperthermia > 40, tachypnoea, tachycardia, diaphoresis, mydriasis (pupillary dilation)

Can proceed to rhabdomyolysis –> kidney then needs to filter breakdown product of muscle (myoglobin) which can induce AKI

Causes of serotonin syndrome: SSRI/SNRI/ MAOI’s - careful with switching SSRI’s, ensure washout before starting new one.

Illegal drugs - methamphetamins, cocaine, MDMA

Tx- cooling, fluid resucitation and dialysis for AKI

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12
Q

What is a drug fever?

A

Drug fever = fever coinciding with administration of a drug, disappearing after the discontinuation of the drug when no other cayse for the fever is evident.

5 Categories - hypersensitivity reactions, altered thermoregulatory mechanisms, reaction to adminstration method, reactions direct extension of normal drug effect, idiosyncratic reactions

Idiosyncratic reactions include:

1) malignant hyperthermia - in response to GA - sudden onset muscle rigidity, metabolic acidosis, haemodynamic instability
2) neuroepileptic malignant syndrome - dopamine depleting agents e.g. haloperidol - high fever, muscle rigidity, altered mental state,
3) serotonin syndrome - excess 5HT

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13
Q

Identify and classify common/ important causes of fever and understand demographics/ RF’s associated with each cause:

Polymyalgia rhematica:

Who commonly presents with this/ Rf’s?

A
  • Polymyalgia rheumatica - inflammatory rheumatological syndrome manifesting as pain/ morning stiffness, involving the neck/ shoulder/ pelvis in individuals > 50 yrs. May have peripheral MSK involvement too.
  • Risk factors:
    • Female
    • giant cell arteritis- 15-20% present w this (inflammation of the arteries within head - commonly temporal - can lead to blindness!)
    • age > 50 yrs
  • often acute onset, low grade fever, weight loss/ anorexia, general malaise, PLUS shoulder/ hip stiffness and pain, there is a rapid response to corticosteroids
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14
Q

Identify and classify common/ important causes of fever and understand demographics/ RF’s associated with each cause:

SLE

A

SLE = chronic multi system disorder - most commonly affecting women during reproductive years.

Characterised by presence of antinuclear antibodies

Involves skin and joints, serositis, nephritis and haemotological cytopenias, neurological manifesations can occur.

Key diagnostic features: malar (butterfly) rash, photosensitive rash, discoid rash. Plus fatigue/WL/fever/ ulcers/ arthraligia/ lymphadenopathy/ HTN

RF’s: Female, age 15-45 yrs, african/asian descent in europe and US, drugs (AE: carbamazepine, phenytoin, DMARD - sulfasalazine)

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15
Q

Identify and classify common/ important causes of fever and understand demographics/ RF’s associated with each cause:

Rheumatoid arthritis

A
  • RA = chronic inflammatory erosive arthritis primarily affecting the small joints of the hands and feet.
  • Diagnostic factors = active symmetrical arthritis lasting > 6 weeks, age 50-55yrs, female, joint pain and swelling (commonly metacarpophalangeal, proximal interphalangeal, metatarsophalangeal). (wrist/elbow/ankles can also be affected), morning stiffness > 1 hr
  • Risk factors:
    • FHx of RA
    • Female
    • age 50 - 55yrs
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16
Q

Key features of fever history?

A
  • Have they measured temp at home?
  • Is there a pattern to the temperature?
    • Tertian and quartan fever in malaria
    • Tertian - fever for a day whilst malaria larvae attach to RBC, gorw, and burst causing inflammation, then fever subsides as they enter the liver to reproduce (quartan similar, fever for a day, returns in three days).
  • Associated symptoms:
    • Joint pain - arthritis
    • Chest pain - endocarditis
    • Rashes? –> target lesions in lymes dsease, generalised cutaneous eruptions in drug reactions
    • haemoptysis - TB or malignancy
  • Full systems enquiry:
    • WL: malignangy/ HIV/TB/ endocarditis
    • Lumps: malignancy or abscess
    • lymphadenopathy: abscess, HIV, malignancy
  • Travel history:
    • Where - any malaria endemic areas (SE asia, subsaharan africa, ZIKA in South america, TB edemic areas?)
    • How long for
    • vaccination history/ antimalarials whilst they were there?
    • what did they do - hiking and lyme disease, swimming in open water (schistomiasis in lake malawi), tattoos and sexual encounters
  • PMH - immunosuppresion?
  • Drug Hx: any new medications (drug fever), immunosuppresion (steroids/DMARDS etc), vaccinations?
  • Past surgical hx - infected prosthesis or collection?
  • Sexual Hx - HIV/hepatitis/syphyllis/ PID
  • Social Hx:
    • RF’s –> malignancy & smoking, alcohol,
    • Occupation: exposure to asbestos (bulders/ plumbers/ mining/ shipyards), pigeons lung = pulm fibrosis reaction to bird faeces/feathers, brucellosis w livestock, leptospirosis w rats
    • Illicit drug use –> serotonin syndrome
17
Q

Key features of examination in fever?

A
  • Examine head to toe but specifically:
    • Head and neck exam - Sinusitis/ oral lesions associated w autoimmune or infectious disorder (candiasis HIV), temporal artery tenderness (GCA)
    • Heart - New murmurs - endocarditis
    • Lungs - pneumonia
    • joints - SLE/RA/polymyalgia rhematica
    • abdominal tenderness - intraabdominal infection or IBD
    • Hepato or splenomegaly - malignancies or autoimmune disorders
    • Lymphadenopathy - infection or maligancy (lymphoma or disseminated TB)
    • janeway lesions/ oslers nodes (Pathophysiology of splinter haemorrhage / Janeway lesions à septic emboli (infected emboli) -> shoot off and block capillaries in the peripheries à if throw off emboli that are big enough you can get necrotic toes)
    • roth spots fundoscopy - red spots - microemboli in retina - endocarditis
    • skin - rashes?
      • butterfly/ malar rash/ discoid/ SLE
      • HIV - atopic dermatitis, dryness, seborrheic dermatitis
      • Epstein barr - maculopapular rash
    • Temperature pulse disparity (Normally rise 8bpm per degree, exception - relative bradycardia- can be caused by typhoid/brucellosis/ legionellosis
18
Q

Key investigations for fever?

A
  • Bedside:
    • Observations - temp/ HR/RR/BP/Cap refill/
    • Fever diary
    • Sputum culture
    • Urine - MSU and culture
    • ECG
  • Bloods:
    • FBC - Raised WBC
    • U&E’s - AKI/ baseline/ drugs
    • BBV - blood borne virus screen - HIV/hepB/hepC
    • LFT’s - liver disease/ baseline
    • CRP- acute phase reactant raised
    • ESR - giant cell arteritis and long term inflammatory conditions
    • Blood cultures
    • serology - rule out collagen vascular diseases e.g RA/SLE/polymyalgia rheumatica
    • serology - EBV/CMV/toxoplasmosis/brucellosis
  • Imaging:
    • CXR - pneumonia
    • Xray of joint
    • Echo - suspicious of endocarditis
    • CT chest abdomen and pelvis if suspicous of malignancy
    • MRI - osteomyelitis
  • Special tests:
    • joint aspiration/ abscess aspiration
    • Lymph node biopsy
    • liver biopsy
    • LP
19
Q

Management of FUO?

A
  • Specific treatment if a cause has been identified (e.g. carbimazole in thyrotoxicosis etc)
    • do not start empirial Abx or steroid treatment unless large degree of suspicion for infection/pt neutropenic/ immunocompromised or steroids w giant cell arteritis
    • diagnsotic trail of NSAID - more likely to respond if malignant or autoimmune
  • In patient where cause unknown but clinically stable
    • watchful waiting - reassess hx and exam
20
Q

What are the acute phase proteins?

A

APP - proteins that change serum concentration by > 25% in response to inflammatory cytokines - IL1/IL6/TNFa

Positive acute phase proteins increase conc by 25% in response to inflammation, negative APP decrease conc by 25% in response.

Positive: CRP, complement C2/C4, serum amyloid A

Negative: Albumin (production falls to allow AA’s for positive APP production), transferrin

21
Q

Common causes of FUO in adults?

A